Human retroviruses are emerging as etiologic agents of human malignancies. Human T-lymphotropic Virus Type I (HTLV-I) is linked to adult T-cell leukemia (ATL). Human immunodeficiency virus, (HIV, formerly HTLV-III/LAV) the etiologic agent of the acquired immunodeficiency syndrome (AIDS), is associated with Kaposi's sarcoma and certain forms of Hodgkin's lymphoma. Our research is focused on characterizing the relationship of this class of virus to human malignancy. Results of our studies document the spectrum of ATL and modes of spread of HTLV-I by heterosexual and homosexual contact and suggest early life transmission in the household. An indirect etiologic mechanism of carcinogenesis is also suggested for HTLV-I in B-cell chronic lymphocytic leukemia (B-CLL), and for HIV in studies of Hodgkin's and non-Hodgkin's lymphoma and Kaposi's sarcoma. A major focus of HIV research has been on cohorts at high-risk for AIDS followed longitudinally since the very beginning of the AIDS epidemic. Results of studies have documented major modes of transmission of HIV in homosexual men, in hemophiliacs, and in drug users and their heterosexual partners, and from mother to offspring. The natural history of progression, the predictors of risk, and the incidence of various outcomes have been defined. Low T-helper cell counts are predictive of AIDS risk and may contribute to heightened transmission of HIV. Among various cofactors, an immunogenetic marker appears to be associated with heightened AIDS risk. Studies are ongoing to utilize epidemiologic approaches to search for persons infected with related viruses, as well as to support work evaluating the human B-cell lymphotrophic virus (HBLV).